Background and purpose: We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. Methods: We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0mmol/l) were randomized to metformin, in a daily dose of 2g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. Results: Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71mmol/l; 95% CI -0·36 to 1·78). Conclusions: Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.

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International Journal of Stroke
Department of Neurology

den Hertog, H., Vermeer, S., Zandbergen, A., Achterberg, S., Dippel, D., Algra, A., … Koudstaal, P. (2015). Safety and feasibiLIty of Metformin in patients with Impaired glucose Tolerance and a recent TIA or minor ischemic stroke (LIMIT) trial - a multicenter, randomized, open-label phase II trial. International Journal of Stroke, 10(1), 105–109. doi:10.1111/ijs.12023